How Gut Bugs Make You Sick — or Well

You are not alone – ever. All day, every day, you’re in the company of millions of other creatures, even when there’s not another soul in sight. More unsettling still, those unseen others live inside you.

The invisible population that calls you home is known as your microbiome — the millions of nonhuman cells that populate your body, particularly your intestines and other parts of your digestive system. If you could extract them all, they’d fill a half gallon jug. And if you could count them all, they’d outnumber your own cells 10 to 1. The only reason they don’t outweigh us 10 to 1 too is that our own cells are much larger than the bugs are.

Our surprisingly complex internal ecology has been a hot topic in medicine lately. Initiatives such as the Human Microbiome Project, an extension of the Human Genome Project, have been working tirelessly to probe potential links between the human microbiota and human health, and to construct strategies for manipulating the bacteria so that they work with us rather than against us. Much of the time, our gut bugs are indeed more helpmates than invaders. They’re essential to the digestive process and they can boost the immune system by regulating the population of certain immune cells and preventing autoimmunity. But like all long-term house guests, the bugs can also make a mess. They’ve been linked to a range of nasty conditions, including obesity, arthritis, and high cholesterol. Now, two newer areas of research are pushing the field even further, looking at the possible gut bug link to a pair of very different conditions: autism and irritable bowel disease.

Autism research has been the victim of junk science for a long time, principally as a result of the fanciful — and scientifically disproven — idea that the condition is caused by vaccines. That makes it harder for serious scientists to look at other, seeming improbable causes of the condition like the microbiome, at least without raising a lot of skepticism. Making things worse, the seminal, and discredited, study in the autism-vaccine mess suggested that traces of vaccine-related measles virus could be found in the guts of autistic kids, further muddying legitimate study of any real gut-bug connection.

Now, however, the research is emerging from under that cloud, and while no one has established a direct link between gut bacteria and autism just yet, the findings so far are intriguing. Up to 85 percent of children with autism also suffer from some kind of gastrointestinal distress such as chronic constipation or inflammatory bowel disease. Research published in 2005 in the Journal of Medical Microbiology and in 2004 in Applied Environmental Microbiology reported that the stools of autistic children contained higher levels of the bacterium Clostridium, while two 2010 studies in the Journal of Proteome ResearchandNutritional Neuroscience reported unusual levels of metabolic compounds in autistic children’s urine consistent with the high bacterial levels found in the stools of autistic patients. In 2011, a study published in Proceedings of the National Academy of Sciences found that mice with essentially germ-free guts showed abnormal movement and anxiety symptoms, suggesting that at least some active intestinal biome is essential for normal development.

“Until a little while ago it was outlandish to suggest that microbiomes in the gut could be behind this disease,” University of Guelph assistant professor of biology Emma Allen-Vercoe said. “But I think it’s an intersection between the genetics of the patient and the microbiome and the environment.”

For Ellen Bolte, pushing doctors to consider the possibility of a microbiome-autism link has been an uphill battle. Bolte, whose son Andrew was diagnosed with autism in 1994, wondered whether her child’s condition could be caused by a bacterial infection by a Clostridium species after reviewing the early medical literature that she felt supported her hypothesis. Fifteen months and 37 doctors later, Bolte found a doctor willing to test her hypothesis by treating her son with the oral antibiotic Vancomycin, an antibiotic effective against the Clostridia. Andrew began to improve dramatically — enough that Bolte’s story is now profiled in the PBS documentary “The Autism Enigma,” which was aired overseas and just went on sale in the U.S. on DVD.

Bolte’s story is compelling and may signal a profound truth about the roots of autism, but it may also be something else entirely. It’s hard to tell the difference between mere correlation and true causation in cases of recovery like these, and much of the rubbish that passed for science in the vaccines debate involved just this kind of account — often involving chelation that supposedly cleared the body of toxic vaccine ingredients and cured the autism in the bargain. But Bolte’s case has gotten closer, more respectable study. Dr. Sydney Finegold, an emeritus professor of medicine at UCLA, ran a small trial with 10 autistic children and found that eight of them showed improved behavior and communication skills with Vancomycin treatment. They relapsed after they stopped taking the drug. Finegold is also examining a bacterium called Desulfovibrio, a virulent organism that tests have found in about half of patients with autism, but in none of the patients without it.

A study in last week’s issue of Science took the gut bug work in a different direction, looking at the role it may play in inflammatory bowel disease (IBD). IBD is a collection of conditions including ulcerative colitis and Crohn’s disease that affect as many as 1.4 million Americans. Typically, the human immune system does a good job of recognizing alien gut bugs that serve a healthy function or are at least harmless, and gives them an immunological pass. But sometimes that process can go awry.

A team led by National Institute of Allergy and Infectious Disease postdoctoral researcher Timothy Hand infected mice with a parasite called Toxoplasma gondii, which has been associated with numerous deaths by food-borne illness. The parasite, they found, could stimulate the mice’s immune system to go on the offensive—which is exactly what’s supposed to happen. But the immune system also overreacted, attacking not just the Toxoplasma gondii, but also friendly gut bugs that had done no harm. And even after the parasite had been beaten, the immune system’s memory cells continued to recognize the good bugs as invaders, waging a permanent war on them that could prevent the mice from ever fully recovering. If something similar happens in humans — either with Toxoplasma gondii or another invader — it could go a long way to explaining both the existence and persistence of all of the IBD conditions.

Microbiome research is surely in its early stages and cures or treatments based on it are still a good way off. Still, scientists such as Allen-Vercoe are looking at ways to manipulate our internal ecosystems, with different kinds of probiotics or healthy bugs that could help rebalance the microbial population. They’re even looking at the singularly counterintuitive idea of fecal transplants — which are just what they sound like, but could do a lot of good by introducing a healthy biome into a body with an unhealthy one. No surprise, this isn’t the kind of therapy you’d prescribe casually.

“If you have a patient who doesn’t eat meat, you wouldn’t want to give them the ecosystem of a meat-eater,” says Allen-Vercoe. “We want to develop a range of ecosystems from a range of healthy people, and fit patient lifestyle to donor lifestyle.”

Your lifestyle, of course, becomes the lifestyle of all the critters that live within you, and it’s in our best interests to keep them all happy. Like it or not, a bunch of bugs constitutes a huge part of who you are. That realization gives medicine a whole new degree of complexity — as well as a whole new degree of promise.